MOLECULAR ANALYSIS OF PHOTOTRANSDUCTION

我们感兴趣的是更深入地了解组件， 调节光转导级联反应，并了解扰动如何 在光感受器细胞生理学中导致各种形式视网膜 退化我们用果蝇的视觉系统来研究这些广泛的 问题.果蝇是服从分子，电生理， 用遗传学方法鉴定分子并在体内研究蛋白质 生物化学途径的关系。因为许多无脊椎动物的视觉 转导蛋白具有脊椎动物同源物，两个级联都可以起作用 以类似的方式。因此，分子的鉴定和 果蝇中的机制可能阐明脊椎动物的视觉转导 通路许多视觉传导分子表现出视网膜变性 在无脊椎动物或脊椎动物中发生改变。因此研究 这些分子在视觉传导中的作用将阐明 导致退化的机制。 我们将扩展我们对果蝇视网膜变性-B（rdgB）的分析， 其表现出光感受器的光依赖性退化。rdgB 蛋白是一种新的磷脂酰肌醇转移蛋白（PI-TP）， 在视觉传导级联中。PI-TP的一个定义角色是 囊泡运输的调节。rdgB蛋白的免疫定位 在横纹肌胞质面附近的蛋白质与 在囊泡运输从trans-Golgi室到 横纹肌rdgB多克隆抗血清染色脊椎动物杆内 节，这表明脊椎动物的“光感受器”同源物的存在。 果蝇分子的详细分析和 脊椎动物同源物可以阐明杆外盘组装的各个方面， 可能是一种新型的视网膜退化 dgq基因编码两种果蝇感光器特异性G蛋白， 亚基DGq 1和DGq 2。我们从基因和生化方面证明了 DGq 1参与了光激活途径。进一步分析 将揭示什么是DGq 1的效应分子和DGq 2在 光转导级联此外，一个类似的显性突变， DGq 1和转导蛋白都导致异常的适应反应， 果蝇和小鼠。因此，进一步的基因和 DGq 1的分子分析可能阐明一个共同的适应机制， 包括脊椎动物和无脊椎动物。

We are interested in a deeper understanding of the components and regulation of the phototransduction cascade and learning how perturbations in photoreceptor cell physiology lead to various forms of retinal degeneration. We use the Drosophila visual system to examine these broad questions. Drosophila is amenable to molecular, electrophysiological, and genetic approaches to identify molecules and to study in vivo the protein relationships in biochemical pathways. Because many invertebrate visual transduction proteins have vertebrate homologs, both cascades may function in an analogous manner. Thus, the identification of molecules and mechanisms in Drosophila may clarify the vertebrate visual transduction pathway. Many visual transduction molecules exhibit retinal degeneration when altered in either invertebrates or vertebrates. Therefore, studying the role of these molecules in visual transduction will elucidate the mechanisms leading to degeneration. We will extend our analysis of Drosophila retinal degeneration-B (rdgB), which exhibits light-dependent degeneration of photoreceptors. The rdgB protein is a novel phosphatidylinositol transfer protein (PI-TP) required in the visual transduction cascade. One defined role for PI-TPs is regulation of vesicular transport. Immunolocalization of the rdgB protein near the cytosolic face of the rhabdomeres is consistent with the protein functioning in vesicular transport from a trans-Golgi compartment to the rhabdomeres. The rdgB polyclonal antiserum stains vertebrate rod inner segments, suggesting that a vertebrate "photoreceptor" homolog exists. Detailed analysis of the Drosophila molecule and identification of the vertebrate homolog could elucidate aspects of rod outer disc assembly and possibly a novel form of retinal degeneration. The dgq gene encodes two Drosophila photoreceptor-specific G-protein a subunits, DGq1 and DGq2. We demonstrated genetically and biochemically that DGq1 is involved in the light-activated pathway. Further analyses will reveal what is DGq1 's effector molecule and the role of DGq2 in the phototransduction cascade. In addition, an analogous dominant mutation in both DGq1 and transducin leads to an abnormal adaptation response in Drosophila and mouse, respectively. Therefore, further genetic and molecular analyses of DGq1 may elucidate a common adaptation mechanism in both vertebrates and invertebrates.